An Integrated Encyclopedia of DNA Elements in the Human Genome

Overview

Journal Nature

Specialty Science

Date 2012 Sep 8

PMID 22955616

Citations 9239

Affiliations

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Abstract

The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research.

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References

Schultz D, Ayyanathan K, Negorev D, Maul G, Rauscher 3rd F . SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins. Genes Dev. 2002; 16(8):919-32. PMC: 152359. DOI: 10.1101/gad.973302. View

Hoffman M, Buske O, Wang J, Weng Z, Bilmes J, Noble W . Unsupervised pattern discovery in human chromatin structure through genomic segmentation. Nat Methods. 2012; 9(5):473-6. PMC: 3340533. DOI: 10.1038/nmeth.1937. View

Sandelin A, Carninci P, Lenhard B, Ponjavic J, Hayashizaki Y, Hume D . Mammalian RNA polymerase II core promoters: insights from genome-wide studies. Nat Rev Genet. 2007; 8(6):424-36. DOI: 10.1038/nrg2026. View

Boyle A, Hong E, Hariharan M, Cheng Y, Schaub M, Kasowski M . Annotation of functional variation in personal genomes using RegulomeDB. Genome Res. 2012; 22(9):1790-7. PMC: 3431494. DOI: 10.1101/gr.137323.112. View

Koch F, Fenouil R, Gut M, Cauchy P, Albert T, Zacarias-Cabeza J . Transcription initiation platforms and GTF recruitment at tissue-specific enhancers and promoters. Nat Struct Mol Biol. 2011; 18(8):956-63. DOI: 10.1038/nsmb.2085. View

Li B, Carey M, Workman J . The role of chromatin during transcription. Cell. 2007; 128(4):707-19. DOI: 10.1016/j.cell.2007.01.015. View

Kouzarides T . Chromatin modifications and their function. Cell. 2007; 128(4):693-705. DOI: 10.1016/j.cell.2007.02.005. View

Schmidt D, Wilson M, Ballester B, Schwalie P, Brown G, Marshall A . Five-vertebrate ChIP-seq reveals the evolutionary dynamics of transcription factor binding. Science. 2010; 328(5981):1036-40. PMC: 3008766. DOI: 10.1126/science.1186176. View

Neph S, Vierstra J, Stergachis A, Reynolds A, Haugen E, Vernot B . An expansive human regulatory lexicon encoded in transcription factor footprints. Nature. 2012; 489(7414):83-90. PMC: 3736582. DOI: 10.1038/nature11212. View

10.

Borneman A, Gianoulis T, Zhang Z, Yu H, Rozowsky J, Seringhaus M . Divergence of transcription factor binding sites across related yeast species. Science. 2007; 317(5839):815-9. DOI: 10.1126/science.1140748. View

11.

Hesselberth J, Chen X, Zhang Z, Sabo P, Sandstrom R, Reynolds A . Global mapping of protein-DNA interactions in vivo by digital genomic footprinting. Nat Methods. 2009; 6(4):283-9. PMC: 2668528. DOI: 10.1038/nmeth.1313. View

12.

Asthana S, Noble W, Kryukov G, Grant C, Sunyaev S, Stamatoyannopoulos J . Widely distributed noncoding purifying selection in the human genome. Proc Natl Acad Sci U S A. 2007; 104(30):12410-5. PMC: 1941483. DOI: 10.1073/pnas.0705140104. View

13.

Abecasis G, Altshuler D, Auton A, Brooks L, Durbin R, Gibbs R . A map of human genome variation from population-scale sequencing. Nature. 2010; 467(7319):1061-73. PMC: 3042601. DOI: 10.1038/nature09534. View

14.

Birney E, Stamatoyannopoulos J, Dutta A, Guigo R, Gingeras T, Margulies E . Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature. 2007; 447(7146):799-816. PMC: 2212820. DOI: 10.1038/nature05874. View

15.

Gross D, Garrard W . Nuclease hypersensitive sites in chromatin. Annu Rev Biochem. 1988; 57:159-97. DOI: 10.1146/annurev.bi.57.070188.001111. View

16.

Pei B, Sisu C, Frankish A, Howald C, Habegger L, Mu X . The GENCODE pseudogene resource. Genome Biol. 2012; 13(9):R51. PMC: 3491395. DOI: 10.1186/gb-2012-13-9-r51. View

17.

Cheng C, Alexander R, Min R, Leng J, Yip K, Rozowsky J . Understanding transcriptional regulation by integrative analysis of transcription factor binding data. Genome Res. 2012; 22(9):1658-67. PMC: 3431483. DOI: 10.1101/gr.136838.111. View

18.

Kapranov P, Cheng J, Dike S, Nix D, Duttagupta R, Willingham A . RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science. 2007; 316(5830):1484-8. DOI: 10.1126/science.1138341. View

19.

King M, Wilson A . Evolution at two levels in humans and chimpanzees. Science. 1975; 188(4184):107-16. DOI: 10.1126/science.1090005. View

20.

Landt S, Marinov G, Kundaje A, Kheradpour P, Pauli F, Batzoglou S . ChIP-seq guidelines and practices of the ENCODE and modENCODE consortia. Genome Res. 2012; 22(9):1813-31. PMC: 3431496. DOI: 10.1101/gr.136184.111. View